Stage-specific transcripts of the Plasmodium falciparum pfmdr 1 gene. 1993

S K Volkman, and C M Wilson, and D F Wirth
Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115.

Genes have been identified in Plasmodium falciparum which belong to the ATP-binding cassette superfamily of transport systems based upon sequence and structural homology. One of these genes, the pfmdr 1 gene, is homologous to the mammalian mdr 1 gene, which encodes the P-glycoprotein product. Strong phenotypic data suggests the involvement of a P-glycoprotein-like molecule in the mediation of drug resistance in P. falciparum. The goal of this work was to characterize the expression of the pfmdr 1 messenger RNA: both the stage specific expression and the level of expression in mefloquine sensitive or resistant parasites. We identified two messenger RNA homologous to this gene, one of 8.5 kb expressed in ring and trophozoite stages, and a second messenger RNA of 7.5 kb expressed only in trophozoites. Previously we had reported an increased expression of messenger RNA for pfmdr 1 in a mefloquine-resistant clone. Here we extend this and demonstrate that overexpression of the pfmdr 1 gene is consistent with the mefloquine resistance phenotype in a panel of recent isolates from Thailand.

UI MeSH Term Description Entries
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D010963 Plasmodium falciparum A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics. Plasmodium falciparums,falciparums, Plasmodium
D011061 Poly A A group of adenine ribonucleotides in which the phosphate residues of each adenine ribonucleotide act as bridges in forming diester linkages between the ribose moieties. Adenine Polynucleotides,Polyadenylic Acids,Poly(rA),Polynucleotides, Adenine
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D015767 Mefloquine A phospholipid-interacting antimalarial drug (ANTIMALARIALS). It is very effective against PLASMODIUM FALCIPARUM with very few side effects. Lariam,Mefloquine Hydrochloride,Mephloquine,Ro-21-5998-001,WR-142,490,WR-177,602,Ro 21 5998 001,Ro215998001,WR 142,490,WR 177,602,WR142,490,WR177,602
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D016053 RNA, Protozoan Ribonucleic acid in protozoa having regulatory and catalytic roles as well as involvement in protein synthesis. Protozoan RNA

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